ANTI-TERMINATION OF TRANSCRIPTION WITHIN THE LONG TERMINAL REPEAT OF HIV-1 BY TAT GENE-PRODUCT
ANTI-TERMINATION OF TRANSCRIPTION WITHIN THE LONG TERMINAL REPEAT OF HIV-1 BY TAT GENE-PRODUCT
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DOI：
10.1038/330489a0
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发表时间：
1987-12-03
期刊：
影响因子：
64.8
通讯作者：
PETERLIN, BM
中科院分区：
文献类型：
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作者：
KAO, SY;CALMAN, AF;PETERLIN, BM
人类免疫缺陷病毒-1 （HIV-1）基因的表达受细胞转录因子和病毒编码的HIV-1tatandart/trsgenes的反式激活蛋白控制，这对病毒复制至关重要1,9 - 11。Tat通过与位于HIV-1长末端重复序列（LTR）中的反式反应元件（TAR）相互作用激活HIV-1基因表达（参考文献2）。在瞬时表达试验中，其作用主要是通过在其5 '端或其附近增加含有TAR序列的信使RNA物种的稳态水平来调节的，这表明其在转录或随后的RNA加工中具有功能。该基因还可以促进含有TAR序列5 - 8的mRNA的翻译。为了确定反式激活的机制，我们分析了HIV-1 LTR在存在和不存在LTR的瞬时表达试验中指导的RNA种类的结构和合成速率。尽管HIV-1的转录起始率不受其影响，但只有在存在这种情况下，转录延伸才会超过+59位。因此，它通过解除TAR序列中特定的转录延伸阻滞来激活HIV-1转录。
Human immunodeficiency virus-1 (HIV-1) gene expression is controlled by cellular transcription factors and by virally encodedtrans-activation proteins of the HIV-1tatandart/trsgenes, which are essential for viral replication1,9–11.Tat trans-activates HIV-1 gene expression by interacting with the trans-acting response element (TAR) located within the HIV-1 long terminal repeat (LTR) (ref. 2). In transient expression assays,tatmediates its effects largely by increasing the steady-state levels of messenger RNA species that contain the TAR sequence at or near their 5′ ends2–4, suggesting a function fortateither in transcription or in subsequent RNA processing. Thetatgene could also facilitate translation of mRNA containing the TAR sequence5–8. To determine the mechanism oftrans-activation bytat, we analysed the structure and rate of synthesis of RNA species directed by the HIV-1 LTR in transient expression assays both in the presence and absence oftat. Although the rate of HIV-1 transcription initiation was not affected bytat, transcriptional elongation beyond position +59 was seen only in the presence oftat. Thus,tat trans-activates HIV-1 transcription by relieving a specific block to transcriptional elongation within the TAR sequence.